Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1

XRCC1 protein is required for the repair of DNA single‐strand breaks and genetic stability, and is essential for viability in mammals. XRCC1 functions as a scaffold protein by interacting and modulating polypeptide components of the single‐strand break repair machinery, including AP endonuclease‐1,...

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Bibliographic Details
Published in:The EMBO journal 2002-09, Vol.21 (17), p.4741-4748
Main Authors: Iftner, Thomas, Elbel, Michaela, Schopp, Betti, Hiller, Thomas, Loizou, Joanna I., Caldecott, Keith W., Stubenrauch, Frank
Format: Article
Language:English
Subjects:
Adenosine diphosphate
Animals
ber
Cell Transformation, Viral - genetics
CHO Cells
Cricetinae
Cricetulus
Deoxyribonucleic acid
DNA
DNA Damage
DNA Repair
DNA, Single-Stranded - genetics
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Drug Resistance - genetics
EMBO13
EMBO23
HPV E6
Humans
Methyl Methanesulfonate - pharmacology
Mutagens - pharmacology
Oncogene Proteins, Viral - metabolism
Oncogene Proteins, Viral - pharmacology
Papillomaviridae - pathogenicity
Protein Binding
Recombinant Fusion Proteins - physiology
Repressor Proteins
strand break repair
Transfection
Two-Hybrid System Techniques
X-ray Repair Cross Complementing Protein 1
XRCC1
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Summary:XRCC1 protein is required for the repair of DNA single‐strand breaks and genetic stability, and is essential for viability in mammals. XRCC1 functions as a scaffold protein by interacting and modulating polypeptide components of the single‐strand break repair machinery, including AP endonuclease‐1, DNA ligase IIIα, poly (ADP‐ribose) polymerase, DNA polymerase β and human polynucleotide kinase. We show here that the E6 protein of human papillomavirus type 1, 8 and 16 directly binds XRCC1. When tested in CHO derived XRCC1 ‘knock out’ EM9 cells, co‐expression of human papillomavirus 16 E6 with human XRCC1 reduced the ability of the latter protein to correct the methyl methane sulfate sensitivity of XRCC1 mutant CHO cell line EM9. These data identify a novel link between small DNA tumour viruses and DNA repair pathways, and suggest a novel explanation for the development of genomic instability in tissue cells persistently infected with papillomaviruses.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/cdf443